Details
Stereochemistry | ACHIRAL |
Molecular Formula | C26H28ClNO |
Molecular Weight | 405.96 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN(C)CCOC1=CC=C(C=C1)C(=C(\CCCl)C2=CC=CC=C2)\C3=CC=CC=C3
InChI
InChIKey=XFCLJVABOIYOMF-QPLCGJKRSA-N
InChI=1S/C26H28ClNO/c1-28(2)19-20-29-24-15-13-23(14-16-24)26(22-11-7-4-8-12-22)25(17-18-27)21-9-5-3-6-10-21/h3-16H,17-20H2,1-2H3/b26-25-
Molecular Formula | C26H28ClNO |
Molecular Weight | 405.96 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
DescriptionSources: http://www.drugbank.ca/drugs/DB00539Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020497s006lbl.pdf
Sources: http://www.drugbank.ca/drugs/DB00539
Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020497s006lbl.pdf
Toremifene is an antineoplastic hormonal agent primarily used in the treatment of advanced breast cancer. Toremifene is a nonsteroidal agent that has demonstrated potent antiestrogenic properties in animal test systems. The antiestrogenic effects may be related to its ability to compete with estrogen for binding sites in target tissues such as breast. Toremifene inhibits the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes the regression of already established DMBA-induced tumors. In this rat model, Toremifene appears to exert its antitumor effects by binding the estrogen receptors. In cytosols derived from human breast adenocarcinomas, Toremifene competes with estradiol for estrogen receptor protein. Toremifene is a nonsteroidal triphenylethylene derivative. Toremifene binds to estrogen receptors and may exert estrogenic, antiestrogenic, or both activities, depending upon the duration of treatment, animal species, gender, target organ, or endpoint selected. The antitumor effect of toremifene in breast cancer is believed to be mainly due to its antiestrogenic effects, in other words, its ability to compete with estrogen for binding sites in the cancer, blocking the growth-stimulating effects of estrogen in the tumor. Toremifene may also inhibit tumor growth through other mechanisms, such as induction of apoptosis, regulation of oncogene expression, and growth factors. Toremifene is used for the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor-positive or receptor-unknown tumors. Toremifene is currently under investigation as a preventative agent for prostate cancer in men with high-grade prostatic intraepithelial neoplasia and no evidence of prostate cancer. Toremifene is marketed in the United States under the brand name Fareston.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL206 |
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Target ID: Thyroid carcinoma cell lines Sources: https://www.ncbi.nlm.nih.gov/pubmed/9448099 |
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Target ID: CHEMBL2362997 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9754928 |
1.2 µM [IC50] | ||
Target ID: Zaire ebolavirus Sources: https://www.ncbi.nlm.nih.gov/pubmed/23785035 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | FARESTON Approved UseFARESTON® is an estrogen agonist/antagonist indicated for the treatment of metastatic breast cancer in postmenopausal women with estrogen-receptor positive or unknown tumors. Launch Date1997 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
414 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7781262 |
120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOREMIFENE blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
722 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9871429 |
120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOREMIFENE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
28.4 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7781262 |
120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOREMIFENE blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
34.1 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9871429 |
120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOREMIFENE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6.2 day EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7781262 |
120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOREMIFENE blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
99 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9871429 |
120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered: |
TOREMIFENE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
400 mg/m2 1 times / day steady, oral MTD Dose: 400 mg/m2, 1 times / day Route: oral Route: steady Dose: 400 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 5 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 5 Sources: Page: 175 |
DLT: Nausea and vomiting, Dizziness... Other AEs: Sweating, Peripheral edema... Dose limiting toxicities: Nausea and vomiting (grade 1-4, 5 patients) Other AEs:Dizziness (grade 1-4, 4 patients) Sweating (grade 1-4, 3 patients) Sources: Page: 175Peripheral edema (grade 1-4, 3 patients) Vaginal discharge (grade 1-4, 0%) Hot flushes (grade 1-4, 2 patients) |
200 mg/m2 1 times / day steady, oral Recommended Dose: 200 mg/m2, 1 times / day Route: oral Route: steady Dose: 200 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 8 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 8 Sources: Page: 175 |
Other AEs: Nausea and vomiting, Dizziness... Other AEs: Nausea and vomiting (grade 1-4, 7 patients) Sources: Page: 175Dizziness (grade 1-4, 2 patients) Sweating (grade 1-4, 2 patients) Peripheral edema (grade 1-4, 2 patients) Vaginal discharge (grade 1-4, 2 patients) Hot flushes (grade 1-4, 1 patient) |
300 mg/m2 1 times / day steady, oral Recommended Dose: 300 mg/m2, 1 times / day Route: oral Route: steady Dose: 300 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 6 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 6 Sources: Page: 175 |
Other AEs: Nausea and vomiting, Dizziness... Other AEs: Nausea and vomiting (grade 1-4, 6 patients) Sources: Page: 175Dizziness (grade 1-4, 4 patients) Sweating (grade 1-4, 3 patients) Peripheral edema (grade 1-4, 4 patients) Vaginal discharge (grade 1-4, 3 patients) Hot flushes (grade 1-4, 4 patients) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Vaginal discharge | grade 1-4, 0% | 400 mg/m2 1 times / day steady, oral MTD Dose: 400 mg/m2, 1 times / day Route: oral Route: steady Dose: 400 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 5 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 5 Sources: Page: 175 |
Hot flushes | grade 1-4, 2 patients | 400 mg/m2 1 times / day steady, oral MTD Dose: 400 mg/m2, 1 times / day Route: oral Route: steady Dose: 400 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 5 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 5 Sources: Page: 175 |
Peripheral edema | grade 1-4, 3 patients | 400 mg/m2 1 times / day steady, oral MTD Dose: 400 mg/m2, 1 times / day Route: oral Route: steady Dose: 400 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 5 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 5 Sources: Page: 175 |
Sweating | grade 1-4, 3 patients | 400 mg/m2 1 times / day steady, oral MTD Dose: 400 mg/m2, 1 times / day Route: oral Route: steady Dose: 400 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 5 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 5 Sources: Page: 175 |
Dizziness | grade 1-4, 4 patients DLT |
400 mg/m2 1 times / day steady, oral MTD Dose: 400 mg/m2, 1 times / day Route: oral Route: steady Dose: 400 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 5 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 5 Sources: Page: 175 |
Nausea and vomiting | grade 1-4, 5 patients DLT |
400 mg/m2 1 times / day steady, oral MTD Dose: 400 mg/m2, 1 times / day Route: oral Route: steady Dose: 400 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 5 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 5 Sources: Page: 175 |
Hot flushes | grade 1-4, 1 patient | 200 mg/m2 1 times / day steady, oral Recommended Dose: 200 mg/m2, 1 times / day Route: oral Route: steady Dose: 200 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 8 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 8 Sources: Page: 175 |
Dizziness | grade 1-4, 2 patients | 200 mg/m2 1 times / day steady, oral Recommended Dose: 200 mg/m2, 1 times / day Route: oral Route: steady Dose: 200 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 8 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 8 Sources: Page: 175 |
Peripheral edema | grade 1-4, 2 patients | 200 mg/m2 1 times / day steady, oral Recommended Dose: 200 mg/m2, 1 times / day Route: oral Route: steady Dose: 200 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 8 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 8 Sources: Page: 175 |
Sweating | grade 1-4, 2 patients | 200 mg/m2 1 times / day steady, oral Recommended Dose: 200 mg/m2, 1 times / day Route: oral Route: steady Dose: 200 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 8 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 8 Sources: Page: 175 |
Vaginal discharge | grade 1-4, 2 patients | 200 mg/m2 1 times / day steady, oral Recommended Dose: 200 mg/m2, 1 times / day Route: oral Route: steady Dose: 200 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 8 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 8 Sources: Page: 175 |
Nausea and vomiting | grade 1-4, 7 patients | 200 mg/m2 1 times / day steady, oral Recommended Dose: 200 mg/m2, 1 times / day Route: oral Route: steady Dose: 200 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 8 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 8 Sources: Page: 175 |
Sweating | grade 1-4, 3 patients | 300 mg/m2 1 times / day steady, oral Recommended Dose: 300 mg/m2, 1 times / day Route: oral Route: steady Dose: 300 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 6 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 6 Sources: Page: 175 |
Vaginal discharge | grade 1-4, 3 patients | 300 mg/m2 1 times / day steady, oral Recommended Dose: 300 mg/m2, 1 times / day Route: oral Route: steady Dose: 300 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 6 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 6 Sources: Page: 175 |
Dizziness | grade 1-4, 4 patients | 300 mg/m2 1 times / day steady, oral Recommended Dose: 300 mg/m2, 1 times / day Route: oral Route: steady Dose: 300 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 6 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 6 Sources: Page: 175 |
Hot flushes | grade 1-4, 4 patients | 300 mg/m2 1 times / day steady, oral Recommended Dose: 300 mg/m2, 1 times / day Route: oral Route: steady Dose: 300 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 6 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 6 Sources: Page: 175 |
Peripheral edema | grade 1-4, 4 patients | 300 mg/m2 1 times / day steady, oral Recommended Dose: 300 mg/m2, 1 times / day Route: oral Route: steady Dose: 300 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 6 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 6 Sources: Page: 175 |
Nausea and vomiting | grade 1-4, 6 patients | 300 mg/m2 1 times / day steady, oral Recommended Dose: 300 mg/m2, 1 times / day Route: oral Route: steady Dose: 300 mg/m2, 1 times / day Sources: Page: 175 |
unhealthy, 38 - 79 years n = 6 Health Status: unhealthy Condition: metastatic breast cancer Age Group: 38 - 79 years Sex: F Population Size: 6 Sources: Page: 175 |
PubMed
Title | Date | PubMed |
---|---|---|
A two-year dietary carcinogenicity study of the antiestrogen toremifene in Sprague-Dawley rats. | 1996 Nov |
|
Structure-activity relationships for triphenylethylene antiestrogens on hepatic phase-I and phase-II enzyme expression. | 1998 Aug 1 |
|
Inhibitory effects of toremifene on N-methyl-N-nitrosourea and estradiol-17beta-induced endometrial carcinogenesis in mice. | 2002 Jun |
|
Estrogenic effects of toremifene and tamoxifen in postmenopausal breast cancer patients. | 2003 Nov |
|
Effect of anti-estrogens on the androgen receptor activity and cell proliferation in prostate cancer cells. | 2004 Dec |
|
Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
Role of 5a-reductase inhibitors and selective estrogen receptor modulators as potential chemopreventive agents for prostate cancer. | 2005 Mar |
|
Drug resistance in chemotherapy for breast cancer. | 2005 Nov |
|
Estrogen receptors as therapeutic targets in breast cancer. | 2006 |
|
Histopathology and histomorphometry of the urogenital tract in 15-month old male and female rats treated neonatally with SERMs and estrogens. | 2006 Aug |
|
Toremifene--a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy. | 2006 Mar |
|
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods. | 2006 Nov |
|
Medicinal chemistry and emerging strategies applied to the development of selective estrogen receptor modulators (SERMs). | 2007 |
|
In silico prediction of pregnane X receptor activators by machine learning approaches. | 2007 Jan |
|
Chemoprevention of prostate cancer: agents and study designs. | 2007 Sep |
Patents
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8350365
Treatment of the human breast cancer cell line MCF-7 with 7.5 uM toremifene for 3 days caused approximately 60% of the cells to exhibit morphologic characteristics typical of cells undergoing apoptosis.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 17:32:03 GMT 2023
by
admin
on
Sat Dec 16 17:32:03 GMT 2023
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Record UNII |
7NFE54O27T
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Record Status |
Validated (UNII)
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Record Version |
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-
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
75393
Created by
admin on Sat Dec 16 17:32:04 GMT 2023 , Edited by admin on Sat Dec 16 17:32:04 GMT 2023
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EMA ASSESSMENT REPORTS |
FARESTON(AUTHORIZED: BREAST NEOPLASMS)
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NDF-RT |
N0000175826
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WHO-VATC |
QL02BA02
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FDA ORPHAN DRUG |
60291
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LIVERTOX |
NBK548338
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NCI_THESAURUS |
C1821
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WHO-ATC |
L02BA02
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NDF-RT |
N0000000168
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3005573
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7NFE54O27T
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m10979
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D017312
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DTXSID3023689
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C1256
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5698
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SUB11197MIG
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TOREMIFENE
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100000089196
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DB00539
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2709
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38409
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9635
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7NFE54O27T
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CHEMBL1655
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89778-26-7
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4325
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